DESCRIPTION: (Adapted from the candidate's description) The overall goal of this application is to elucidate mechanisms making the developing brain uniquely vulnerable to hypoxic ischemic injury. The application is based on the premise that a detailed understanding of normal cortical development may help to determine why different patterns of injury occur at each stage of development. Development of the visual system is used as a model of cortical development. The proposed studies examine the identity of cells injured during development. Then, focusing on a specific population of cells - subplate neurons, the molecular mechanisms mediating early hypoxic ischemic brain injury will be investigated. The primary hypothesis is that subplate neurons are particularly vulnerable to early hypoxic ischemic brain injury. The secondary hypothesis is that mechanisms governing normal subplate neuron cell death contribute to its sensitivity to hypoxic ischemic and excitotoxic cell death. Three specific aims are proposed: 1) To characterize the identity, topography, and time course of dying cells following early hypoxic ischemic brain injury, and to correlate these observations with alterations in normal cortical development; 2) To determine the relationship of subplate neuron cell death to the expression and regulation of receptors for glutamate and neurotrophins; and 3) To identify genes differentially expressed by subplate neurons normally and following hypoxia ischemia brain injury.